A defined subset of adenylyl cyclases is regulated by bicarbonate ion

Cann, M.J.; Hammer, A.; Zhou, J.; Kanacher, T.

Abstract

The molecular basis by which organisms detect and respond to fluctuations in inorganic carbon is not known. The cyaB1 gene of the cyanobacterium Anabaena sp. PCC7120 codes for a multidomain protein with a C-terminal class III adenylyl cyclase catalyst that was specifically stimulated by bicarbonate ion (EC50 9.6 mM). Bicarbonate lowered substrate affinity but increased reaction velocity. A point mutation in the active site (Lys-646) reduced activity by 95% and was refractory to bicarbonate activation. We propose that Lys-646 specifically coordinates bicarbonate in the active site in conjunction with an aspartate to threonine polymorphism (Thr-721) conserved in class III adenylyl cyclases from diverse eukaryotes and prokaryotes. Using recombinant proteins we demonstrated that adenylyl cyclases that contain the active site threonine (cyaB of Stigmatella aurantiaca and Rv1319c of Mycobacterium tuberculosis) are bicarbonate-responsive, whereas adenylyl cyclases with a corresponding aspartate (Rv1264 of Mycobacterium) are bicarbonate-insensitive. Large numbers of class III adenylyl cyclases may therefore be activated by bicarbonate. This represents a novel mechanism by which diverse organisms can detect bicarbonate ion.

Citation

Cann, M., Hammer, A., Zhou, J., & Kanacher, T. (2003). A defined subset of adenylyl cyclases is regulated by bicarbonate ion. Journal of Biological Chemistry, 278(37), 35033-35038. https://doi.org/10.1074/jbc.m303025200

• Journal Article Type: Article
• Publication Date: Sep 12, 2003
• Deposit Date: May 14, 2007
• Publicly Available Date: Nov 27, 2014
• Journal: Journal of Biological Chemistry
• Print ISSN: 0021-9258
• Electronic ISSN: 1083-351X
• Publisher: American Society for Biochemistry and Molecular Biology
• Peer Reviewed: Peer Reviewed
• Volume: 278
• Issue: 37
• Pages: 35033-35038
• DOI: https://doi.org/10.1074/jbc.m303025200
• Public URL: https://durham-repository.worktribe.com/output/1625419